Baker, K. Scott

Burroughs, Lauri

Carpenter, Paul A.

Domm, Jennifer

Englund, Janet A.

Guthrie, Katherine A.

Nemecek, Eneida

Shimamura, Akiko

Skoda-Smith, Suzanne

Storb, Rainer F.

Talano, Julie-An

Torgerson, Troy

Woolfrey, Ann

Elsevier - Publisher Connector 

Treosulfan Based Conditioning Followed by Allogeneic Hematopoietic Cell Transplantation for Treatment of Patients with Non-Malignant Diseases: Preliminary Results of a Phase II Study 

Abstracts / Biol Blood Marrow Transplant 19 (2013) S150eS166S158Conclusions: Both autoHCT and alloHCT are feasible and
provide durable PFS and OS in this high risk cohort. Trans-
formation to DLBCL > 1 year after dx of FL is associated with
improved 1 yr PFS in both autoHCT and alloHCT groups, and
superior 2 yr OS in the alloHCT group compared to those
cases with transformation< 1year from dx of FL. Patients
with primary induction failure also beneﬁt from consolida-
tion with HCT.PEDIATRIC DISORDERS ORAL87
Treosulfan Based Conditioning Followed by Allogeneic
Hematopoietic Cell Transplantation for Treatment of
Patients with Non-Malignant Diseases: Preliminary
Results of a Phase II Study
Lauri Burroughs 1,2, Eneida Nemecek 3, Troy Torgerson 2,
Katherine A. Guthrie 4, Julie-An Talano 5, Jennifer Domm6,
Akiko Shimamura 1,2, Paul A. Carpenter 1,2,
Suzanne Skoda-Smith 2, Janet A. Englund 2, K. Scott Baker 1,2,
Rainer F. Storb 1,2, Ann Woolfrey 1,2. 1 Fred Hutchinson Cancer
Research Center; 2 University of Washington School of
Medicine; 3Oregon Health & Science University; 4 Clinical
Oncology, Fred Hutchinson Cancer Research Center, Seattle,
WA; 5Medical College of Wisconsin; 6 Vanderbilt University
Treosulfan has several characteristics that make it
appealing for use in conditioning, including bypass of
hepatic enzyme activation, a highly predictable pharma-
cokinetic proﬁle, and sufﬁcient immunosuppressive
activity to allow for engraftment of donor cells across
histocompatibility barriers. Here we report the preliminary
results of a phase II multi-center clinical trial for 25
patients with non-malignant diseases [primary immune
deﬁciency diseases (PIDD, n¼12), hemophagocytic lym-
phohistiocytosis (HLH; n¼5), inherited bone marrow
failure syndromes (n¼4), and other non-malignant
diseases (n¼4)] who received allogeneic hematopoietic cell
transplantation (HCT) from October 2009 to July 2012.
Patients were given HLA-matched related (n¼2) or unre-
lated (n¼23) marrow (n¼23) or G-CSF mobilized periph-
eral blood stem cell (n¼2) grafts following conditioning
with treosulfan (total dose: 42 grams/m2), ﬂudarabine
(total dose: 150 mg/m2), +/- thymoglobulin (rabbit ATG,
n¼16; total dose: 6 mg/kg). All patients received tacroli-
mus and methotrexate for GVHD prevention. Median age
at HCT was 8.3 (range, 0.4-30.5) years. Three patients had
received a previous allogeneic HCT. Median time to
neutrophil engraftment was 22 days. Of the 25 evaluable
patients, all had full (>95%; n¼19) or mixed (50-94%, n¼3;
6-49%, n¼3) donor CD3+ T-cell chimerism. One patient
with sickle cell disease who received a very low total
nucleated cell dose required a stem cell boost due to poor
graft function. With a median follow-up for survivors of 12
(range, 2-35) months, the 1-year survival was 86%. Three
patients died; one died from GVHD 5 months after HCT,
one died at 4 months from an unrelated surgical compli-
cation, and one died at 8 months from recurrent CNS HLH.
None of the patients developed sinusoidal obstructive
syndrome. One patient was intubated for airway protec-
tion in the setting of herpes stomatitis. The cumulative
incidence of grades III-IV acute GVHD at 100 days and 1-
year chronic GVHD were 12% and 25%, respectively.
Patients who received ATG had a signiﬁcantly lower inci-
dence of grade III-IV acute GVHD (0% compared to 33%;P ¼ .02). Our results to date indicate that the combination
of treosulfan, ﬂudarabine, and rabbit ATG is effective at
establishing donor engraftment with a low toxicity proﬁle.
These results suggest that the reduction of regimen-
related toxicities will translate into improved survival
outcomes in patients with PIDD and other non-malignant
diseases, and support the need for future disease-speciﬁc
clinical trials.
88
HLA Allele Matched Unrelated Donor Stem Cell
Transplant As First Line Therapy for Children with
Acquired Severe Aplastic Anemia
Jing Chen 1, Vincent Lee 2, Chengjuan Luo 3,
Alan Kwok-Shing Chiang 4, Suradej Hongeng 5, Poh-Lin Tan 6,
Ah-Moy Tan 7, Sanpakit Sanpakit 8, Chun Fu Li 9,
Anselm Chi-wai Lee 10, Hsin Chieh 11. 1 shanghai children's
medical center; 2 Prince of Wales Hospital, Hong Kong;
3 shanghai children's medical center, shanghai; 4 Queen Mary
Hospital, the University of Hong Kong; 5 Pediatrics,
Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;
6 Paediatrics, National University Health System, Singapore,
Singapore, Singapore; 7 Paediatric Medicine, KK Women's and
Children's Hospital, Singapore, Singapore; 8 Department of
Pediatrics Faculty of Medicine Siriraj hospital Mahidol
University; 9 Nanfang Hospital Southern Medical University;
10 Children's Haematology and Cancer Centre Mount Elizabeth
Hospital; 11 National University Health System and Yasuhiro
Okamoto, Kagoshima University Medical and Dental Hospital
From August 2000 to November 2011, 127 children
under the age of 18 years with acquired severe aplastic
anemia (SAA) received hematopoietic stem cell trans-
plantation (HSCT) in one of the 10 Asia Paciﬁc institutions
of the VABMT Consortium, including 53 with matched
sibling donor (MSD) and 74 with alternative donor (AD).
Among these 74 AD, 22 were matched unrelated donor
(MUD), 32 were mismatched unrelated donor (MMUD) and
20 were mismatched related donor (MMRD). Although the
MSD group developed less grade II-IV acute GVHD
compared to the AD group (14.3% vs 32.8%, P ¼ .029), there
was no signiﬁcant difference in grade III-IV GVHD (10.2%
vs 12.5%, P ¼ .774) or chronic GVHD (19.6% vs 35.0%, P ¼
.088). After a median follow-up of 33.5 months, the inci-
dence of graft failure and 3-year overall survival were


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Treosulfan Based Conditioning Followed by Allogeneic Hematopoietic Cell Transplantation for Treatment of Patients with Non-Malignant Diseases: Preliminary Results of a Phase II Study

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